Identification and transcriptome analysis of a photosynthesis deficient mutant of Populus davidiana Dode.

Photosynthesis is the main source of energy for plants to sustain growth and development. Abnormalities in photosynthesis may cause defects in plant development. The elaborate regulatory mechanism underlying photosynthesis remains unclear. In this study, we identified a natural mutant from the Greater Khingan Mountains and named it as "1-T". This mutant had variegated leaf with irregular distribution of yellow and green. Chlorophyll contents and photosynthetic capacity of 1-T were significantly reduced compared to other poplar genotypes. Furthermore, a transcriptome analysis revealed 3269 differentially expressed genes (DEGs) in 1-T. The products of the DEGs were enriched in photosystem I and photosystem II. Three motifs were significantly enriched in the promoters of these DEGs. Yeast one-hybrid, Electrophoretic mobility shift assays and tobacco transient transformation experiments indicated that PdGLKs may bind to the three motifs. Further analysis indicated that these photosystem related genes were also significantly down-regulated in PdGLK-RNAi poplars. Therefore, we preliminarily concluded that the down-regulation of PdGLKs in 1-T may affect the expression of photosystem-related genes, resulting in abnormal photosystem development and thus affecting the growth and development. Our results provide new insights into the molecular mechanism of photosynthesis regulating plant growth.

Association between perfluoroalkyl substances and breast cancer on the National Health and Nutrition Examination Survey Database and meta-analysis.

The relationship between perfluoroalkyl substances (PFASs) and the risk of breast cancer has been controversial. Here, we used the National Health and Nutrition Examination Survey (NHANES) database and a meta-analysis to examine the association between PFASs and breast cancer incidence. From the NHANES database, we obtained data on PFASs and breast cancer from 2003 to 2014. We searched PubMed, Web of Science, Scopus and PsycINFO from the establishment of the databases to August 24, 2023, for research on PFASs related to breast cancer. A meta-analysis was performed using Stata 12.0. A total of 1430 subjects aged 20 years or older were selected from the NHANES. The logistic regression results indicated that there was no correlation between breast cancer and PFASs (P > 0.05). The meta-analysis, included nine studies with a total of 2399 breast cancer patients, included in the meta-analysis, revealed no statistically significant association between PFASs and the risk of breast cancer (odds ratio = 1.04; 95 % confidence interval, 0.88-1.21; P > 0.05). The results show that PFASs are not associated with breast cancer risk.

Design and Synthesis of Thiourea-Conjugating Organic Arsenic D-Glucose with Anticancer Activities.

Organic arsenic compounds such as p-aminophenylarsine oxide (p-APAO) are easier for structural optimization to improve drug-like properties such as pharmacokinetic properties, therapeutic efficacy, and target selectivity. In order to strengthen the selectivity of 4-(1,3,2-dithiarsinan-2-yl) aniline 7 to tumor cell, a thiourea moiety was used to strengthen the anticancer activity. To avoid forming a mixture of α/ß anomers, the strategy of 2-acetyl's neighboring group participation was used to lock the configuration of 2,3,4,6-tetra-O-acetyl-ß-d-glucopyranosyl isothiocyanate from 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide. 1-(4-(1,3,2-dithiarsinan-2-yl) aniline)-2-N-(2,3,4,6-tetra-O-acetyl-ß-d-glucopyranos-1-yl)-thiourea 2 can increase the selectivity of human colon cancer cells HCT-116 (0.82 ± 0.06 µM vs. 1.82 ± 0.07 µM) to human embryonic kidney 293T cells (1.38 ± 0.01 µM vs. 1.22 ± 0.06 µM) from 0.67 to 1.68, suggesting a feasible approach to improve the therapeutic index of arsenic-containing compounds as chemotherapeutic agents.

Pm57 from Aegilops searsii encodes a tandem kinase protein and confers wheat powdery mildew resistance.

Powdery mildew is a devastating disease that affects wheat yield and quality. Wheat wild relatives represent valuable sources of disease resistance genes. Cloning and characterization of these genes will facilitate their incorporation into wheat breeding programs. Here, we report the cloning of Pm57, a wheat powdery mildew resistance gene from Aegilops searsii. It encodes a tandem kinase protein with putative kinase-pseudokinase domains followed by a von Willebrand factor A domain (WTK-vWA), being ortholog of Lr9 that mediates wheat leaf rust resistance. The resistance function of Pm57 is validated via independent mutants, gene silencing, and transgenic assays. Stable Pm57 transgenic wheat lines and introgression lines exhibit high levels of all-stage resistance to diverse isolates of the Bgt fungus, and no negative impacts on agronomic parameters are observed in our experimental set-up. Our findings highlight the emerging role of kinase fusion proteins in plant disease resistance and provide a valuable gene for wheat breeding.

Diagnostic value of exosomal noncoding RNA in lung cancer: a meta-analysis.

Background: Lung cancer is one of the most dangerous cancers in the world. Most lung cancer patients are diagnosed in the middle and later stages, which can lead to poor survival rates. The development of lung cancer is often accompanied by abnormal expression of exosomal non-coding RNAs, which means that they have the potential to serve as noninvasive novel molecular markers for lung cancer diagnosis. Methods: For this study, we conducted a comprehensive literature search in PubMed, Web of science, Science direct, Embase, Cochrane, and Medline databases, and by reviewing published literature, The diagnostic capacity of exosomal microRNAs (miRNAs), long-chain non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) for lung cancer was evaluated. Functional enrichment analysis of miRNA target genes was performed. Results: The study included 41 papers, a total of 68 studies. More than 60 miRNAs, 9 lncRNAs and 14 circRNAs were involved. The combined sensitivity and specificity were 0.83(95%CI, 0.80~0.86) and 0.83(95% CI,0.79~0.87); 0.71(95% CI,0.68~0.74) and 0.79(95%CI, 0.75~0.82); 0.79(95%CI,0.67~0.87) and 0.81(95%CI,0.74~0.86), and constructed overall subject operating characteristic curves with the summarized area under the curve values of 0.90, 0.82, and 0.86. Conclusion: Our study shows that exosomes miRNAs, lncRNAs and circRNAs are effective in the diagnosis of lung cancer, providing evidence for studies related to novel lung cancer diagnostic markers. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023457087.

Isolation and identification of uric acid-dependent Aciduricibacillus chroicocephali gen. nov., sp. nov. from seagull feces and implications for hyperuricemia treatment.

Hyperuricemia has become the second most prevalent metabolic disease after diabetes, but the limitations of urate-lowering treatment (ULT) drugs and patient nonadherence make ULT far less successful. Thus, more ULT approaches urgently need to be explored. Uric acid-degrading bacteria have potential application value in ULT. In this study, we isolated 44XBT, a uric acid-degrading bacterium, from black-headed gull (Chroicocephalus ridibundus) feces. Using a polyphasic taxonomic approach, strain 44XBT was identified as a novel genus within the family Bacillaceae; subsequently, the name Aciduricibacillus chroicocephali was proposed. Strain 44XBT had a unique uric acid-dependent phenotype and utilized uric acid and allantoin as the sole carbon and nitrogen sources, but not common carbon sources or complex media. In the genome, multiple copies of genes involved in uric acid metabolic pathway (pucL, pucM, uraD, and allB) were found. Six copies of pucL (encoding urate oxidase) were detected. Of these, five pucL copies were in a tandem arrangement and shared 70.42%-99.70% amino acid identity. In vivo experiments revealed that 44XBT reduced serum uric acid levels and attenuated kidney damage in hyperuricemic mice through uric acid catalysis in the gut and gut microbiota remodeling. In conclusion, our findings discover a strain for studying bacterial uric acid metabolism and may provide valuable insights into ULT. IMPORTANCE: The increasing disease burden of hyperuricemia highlights the need for new therapeutic drugs and treatment strategies. Our study describes the developmental and application values of natural uric acid-degrading bacteria found in the gut of birds and broadened the source of bacteria with potential therapeutic value. Furthermore, the special physiology characteristics and genomic features of strain 44XBT are valuable for further study.

Gastric mixed neuroendocrine non-neuroendocrine neoplasms.

The uncommon tumour known as gastric mixed neuroendocrine-non-neuroendocrine neoplasms (G-MiNENs) is made up of parts of neuroendocrine carcinoma and adenocarcinoma. The biological and clinical features are different from those of gastric adenocarcinoma. Their pathophysiology, diagnostic standards, and clinical behaviour have all been the subject of lengthy debates, and their nomenclature has undergone multiple changes. Its emergence has created new challenges in the classification and diagnosis of gastric tumours. This review will update information on the topic, covering molecular aspects, diagnostic criteria, treatment, and prognostic factor discovery. It will also provide a historical context that will aid in understanding the evolution of the idea and nomenclature of mixed gastric tumours. Additionally, it will provide the reader a thorough understanding of this difficult topic of cancer that is applicable to real-world situations.

Speciation and Possible Origins of Organosulfur Compounds in Rice Paddy Soils Affected by Acid Mine Drainage.

Although sulfur cycling in acid mine drainage (AMD)-contaminated rice paddy soils is critical to understanding and mitigating the environmental consequences of AMD, potential sources and transformations of organosulfur compounds in such soils are poorly understood. We used sulfur K-edge X-ray absorption near edge structure (XANES) spectroscopy to quantify organosulfur compounds in paddy soils from five AMD-contaminated sites and one AMD-uncontaminated reference site near the Dabaoshan sulfide mining area in South China. We also determined the sulfur stable isotope compositions of water-soluble sulfate (δ34SWS), adsorbed sulfate (δ34SAS), fulvic acid sulfur (δ34SFAS), and humic acid sulfur (δ34SHAS) in these samples. Organosulfate was the dominant functional group in humic acid sulfur (HAS) in both AMD-contaminated (46%) and AMD-uncontaminated paddy soils (42%). Thiol/organic monosulfide contributed a significantly lower proportion of HAS in AMD-contaminated paddy soils (8%) compared to that in AMD-uncontaminated paddy soils (21%). Within contaminated soils, the concentration of thiol/organic monosulfide was positively correlated with cation exchange capacity (CEC), moisture content (MC), and total Fe (TFe). δ34SFAS ranged from -6.3 to 2.7‰, similar to δ34SWS (-6.9 to 8.9‰), indicating that fulvic acid sulfur (FAS) was mainly derived from biogenic S-bearing organic compounds produced by assimilatory sulfate reduction. δ34SHAS (-11.0 to -1.6‰) were more negative compared to δ34SWS, indicating that dissimilatory sulfate reduction and abiotic sulfurization of organic matter were the main processes in the formation of HAS.

Photothermal CO2 Catalysis toward the Synthesis of Solar Fuel: From Material and Reactor Engineering to Techno-Economic Analysis.

Carbon dioxide (CO2), a member of greenhouse gases, contributes significantly to maintaining a tolerable environment for all living species. However, with the development of modern society and the utilization of fossil fuels, the concentration of atmospheric CO2 has increased to 400 ppm, resulting in a serious greenhouse effect. Thus, converting CO2 into valuable chemicals is highly desired, especially with renewable solar energy, which shows great potential with the manner of photothermal catalysis. In this review, recent advancements in photothermal CO2 conversion are discussed, including the design of catalysts, analysis of mechanisms, engineering of reactors, and the corresponding techno-economic analysis. A guideline for future investigation and the anthropogenic carbon cycle are provided.

Wheat powdery mildew resistance gene Pm13 encodes a mixed lineage kinase domain-like protein.

Wheat powdery mildew is one of the most destructive diseases threatening global wheat production. The wild relatives of wheat constitute rich sources of diversity for powdery mildew resistance. Here, we report the map-based cloning of the powdery mildew resistance gene Pm13 from the wild wheat species Aegilops longissima. Pm13 encodes a mixed lineage kinase domain-like (MLKL) protein that contains an N-terminal-domain of MLKL (MLKL_NTD) domain in its N-terminus and a C-terminal serine/threonine kinase (STK) domain. The resistance function of Pm13 is validated by mutagenesis, gene silencing, transgenic assay, and allelic association analyses. The development of introgression lines with significantly reduced chromosome segments of Ae. longissima encompassing Pm13 enables widespread deployment of this gene into wheat cultivars. The cloning of Pm13 may provide valuable insights into the molecular mechanisms underlying Pm13-mediated powdery mildew resistance and highlight the important roles of kinase fusion proteins (KFPs) in wheat immunity.

Role of microfibril angle in molecular deformation of cellulose fibrils in Pinus massoniana compression wood and opposite wood studied by in-situ WAXS.

Upon tensile stress, the spiral cellulose fibrils in wood cell walls rotate like springs with decreasing microfibril angle (MFA), and the cellulose molecules elongate in the chain direction. Compression wood with high MFA and opposite wood with low MFA were comparatively studied by in-situ tensile tests combined with synchrotron radiation WAXS in the present study. FTIR spectroscopy revealed that compression wood had a higher lignin content and fewer acetyl groups. For both types of wood, the lattice spacing d004 increased and the MFA decreased gradually with the increase of tensile stress. At stresses beyond the yield point, cellulose lattice strain depended linearly on macroscopic stress, while the MFA depended linearly on macroscopic strain. The deformation mechanisms of compression wood and opposite wood are not essentially different but differ in their deformation behavior. Specifically, the contribution ratio of lattice strain and cellulose fibril reorientation to macroscopic strain was 0.25 and 0.53 for compression wood, and 0.40 and 0.33 for opposite wood, respectively. Due to the geometric effects of MFA, a greater contribution of cellulose fibril reorientation to the macroscopic deformation was detected in compression wood than in opposite wood.

The coupling of anammox with microalgae-bacteria symbiosis: Nitrogen removal performance and microbial community.

The partial nitrification-anammox process for ammonia nitrogen wastewater treatment requires mechanical aeration to provide oxygen, which is not conducive to energy saving. The microalgae-bacteria symbiotic system (MaBS) has the advantages of low carbon and energy saving in wastewater biological nitrogen removal. Therefore, this study combined the MaBS with an anammox process to provide oxygen, through the photosynthesis of microalgae instead of mechanical aeration. We investigated the nitrogen removal efficiency and long-term operation of a co-culture system comprising microalgae, nitrifying bacteria (NB), denitrifying bacteria (DnB), and anaerobic ammonium-oxidation bacteria (AnAOB) in a sequencing batch reactor without mechanical aeration. The experiment was divided into three steps: firstly, cultivating NB; then, adding three kinds of microalgae which were Chlorella sp., Anabaena sp., and Navicula sp. to the bioreactor to construct a microalgae-bacteria symbiotic system; finally, adding anammox sludge to construct the anammox and microalgae-bacteria symbiosis (Anammox-MaBS) system. The results demonstrated that nitrification, denitrification, and anammox processes were coupled successfully, and the maximum TN removal efficiency of the stable Anammox-MaBS system was 99.51 % when the concentration of the influent NH4+-N was 100 mg/L. The addition of microalgae in ammonia wastewater promoted the enrichment of DnB and AnAOB, which were Denitratisoma, Haliangium, unclassified_Rhodocyclaceae, and Candidatus_Brocadia. Furthermore, the unique biofilm structure could effectively alleviate the photoinhibition of light-sensitive bacteria, which may be the reason for the long-term adaptation of Candidatus_Brocadia to light conditions. This research can provide a low-cost solution to bacterial photoinhibition in the coexistence system of microalgae and bacteria without mechanical aeration, offering theoretical support for low-carbon and energy-efficient treatment of wastewater.

Sulfation on polysaccharides from Zizania latifolia extracted using ultrasound: Characterization, antioxidant and anti-non-small cell lung cancer activities.

Zizania latifolia is a highly nutritious vegetable being praised as "Ginseng in Water". Polysaccharides are the main bioactive ingredients in Z. latifolia, but there have been no reports on the yield- and activity-guided ultrasonic-assisted extraction (UAE), sulfation and anti-non-small cell lung cancer (NSCLC) activity. In this study, Z. latifolia polysaccharides (ZLP) were extracted using UAE under an optimized power, followed by sulfation to give three derivatives (SZLP-1 âˆ¼ 3). After characterization, the antioxidant and anti-NSCLC activities were evaluated. The optimal ultrasonic power for ZLP extraction was screened out to be 300 W, under which the yield was 16.9 ± 2.10 %, and the scavenging rate against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical was 63.3 ± 5.71 %, significantly higher than those of other powers and hot-water extraction. A series of characterizations fully confirmed the sulfated modification of ZLP. Sulfation improved the antioxidation of ZLP and was positively proportional to the degree of substitution (DS), of which SZLP-2 with a DS of 15.1 ± 2.50 elicited strong hydroxyl and DPPH radicals-scavenging capacities. Meanwhile, SZLP-2 also exerted promising anti-NSCLC potency via inhibiting A549 cell proliferation, with a median inhibition concentration (IC50) of 0.57 ± 0.01 mg/mL at 72 h, markedly smaller than that of unmodified ZLP (0.78 ± 0.04 mg/mL). In summary, the yield- and activity-guided UAE led to the ZLP with high yield and strong antioxidation. Further sulfation enhanced the bioactivities and produced the promising SZLP-2, which showed great potential in the development of novel antioxidant and anti-NSCLC drug.

HCMV IE1/IE1mut Therapeutic Vaccine Induces Tumor Regression via Intratumoral Tertiary Lymphoid Structure Formation and Peripheral Immunity Activation in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM), a highly malignant invasive brain tumor, is associated with poor prognosis and survival and lacks an effective cure. High expression of the human cytomegalovirus (HCMV) immediate early protein 1 (IE1) in GBM tissues is strongly associated with their malignant progression, presenting a novel target for therapeutic strategies. Here, the bioluminescence imaging technology revealed remarkable tumor shrinkage and improved survival rates in a mouse glioma model treated with HCMV IE1/IE1mut vaccine. In addition, immunofluorescence data demonstrated that the treated group exhibited significantly more and larger tertiary lymphoid structures (TLSs) than the untreated group. The presence of TLS was associated with enhanced T cell infiltration, and a large number of proliferating T cells were found in the treated group. Furthermore, the flow cytometry results showed that in the treatment group, cytotoxic T lymphocytes exhibited partial polarization toward effector memory T cells and were activated to play a lethal role in the peripheral immunological organs. Furthermore, a substantial proportion of B cells in the draining lymph nodes expressed CD40 and CD86. Surprisingly, quantitative polymerase chain reaction indicated that a high expression of cytokines, including chemokines in brain tumors and immune tissues, induced the differentiation, development, and chemokine migration of immune cells in the treated group. Our study data demonstrate that IE1 or IE1mut vaccination has a favorable effect in glioma mice models. This study holds substantial implications for identifying new and effective therapeutic targets within GBM.

Efficient conversion of propane in a microchannel reactor at ambient conditions.

The oxidative dehydrogenation of propane, primarily sourced from shale gas, holds promise in meeting the surging global demand for propylene. However, this process necessitates high operating temperatures, which amplifies safety concerns in its application due to the use of mixed propane and oxygen. Moreover, these elevated temperatures may heighten the risk of overoxidation, leading to carbon dioxide formation. Here we introduce a microchannel reaction system designed for the oxidative dehydrogenation of propane within an aqueous environment, enabling highly selective and active propylene production at room temperature and ambient pressure with mitigated safety risks. A propylene selectivity of over 92% and production rate of 19.57 mmol mCu-2 h-1 are simultaneously achieved. This exceptional performance stems from the in situ creation of a highly active, oxygen-containing Cu catalytic surface for propane activation, and the enhanced propane transfer via an enlarged gas-liquid interfacial area and a reduced diffusion path by establishing a gas-liquid Taylor flow using a custom-made T-junction microdevice. This microchannel reaction system offers an appealing approach to accelerate gas-liquid-solid reactions limited by the solubility of gaseous reactant.

Exposure to mixtures of PM2.5 components and term premature rupture of membranes: a case-crossover study in Shijiazhuang, China.

This study aims to explore the acute effects of short-term exposure to PM2.5 components and their mixture on PROM. Counts of hospital admissions due to PROM were collected at the Fourth Hospital of Shijiazhuang. The associations between the PROM and PM2.5 components was examined using a time-stratified case-crossover approach. The overall effects of components on TPROM were examined using the BKMR. During the study period 30,709 cases of PROMwere identified. The relative risks and the 95% CI of TPROM were 1.013 (1.002, 1.028) and 1.015 (1.003, 1.028) associated with per interquartile range increase in nitrate and ammonium ion on the current day and they were 1.007 (1.001, 1.013) and 1.003 (1.000, 1.005) on the previous day. The results from the BKMR models showed a higher risk of TPROM was associated with exposure to mixtures, in which, nitrate and organic matter were the main contributors to the overall effect.

Liquid-liquid phase separation in plants: Advances and perspectives from model species to crops.

Membraneless biomolecular condensates play important roles in both normal biological activities and responses to environmental stimuli in living organisms. Liquid‒liquid phase separation (LLPS) is an organizational mechanism that has emerged in recent years to explain the formation of biomolecular condensates. In the past decade, advances in LLPS research have contributed to breakthroughs in disease fields. By contrast, although LLPS research in plants has progressed over the past 5 years, it has been concentrated on the model plant Arabidopsis, which has limited relevance to agricultural production. In this review, we provide an overview of recently reported advances in LLPS in plants, with a particular focus on photomorphogenesis, flowering, and abiotic and biotic stress responses. We propose that many potential LLPS proteins also exist in crops and may affect crop growth, development, and stress resistance. This possibility presents a great challenge as well as an opportunity for rigorous scientific research on the biological functions and applications of LLPS in crops.

The SPL transcription factor TaSPL6 negatively regulates drought stress response in wheat.

Environmental stresses, such as heat and drought, severely affect plant growth and development, and reduce wheat yield and quality globally. Squamosa promoter binding protein-like (SPL) proteins are plant-specific transcription factors that play a critical role in regulating plant responses to diverse stresses. In this study, we cloned and characterized TaSPL6, a wheat orthologous gene of rice OsSPL6. Three TaSPL6 homoeologs are located on the long arms of chromosomes 4A, 5B, and 5D, respectively, and share more than 98% sequence identity with each other. The TaSPL6 genes were preferentially expressed in roots, and their expression levels were downregulated in wheat seedlings subjected to heat, dehydration, and abscisic acid treatments. Subcellular localization experiments showed that TaSPL6 was localized in the nucleus. Overexpression of TaSPL6-A in wheat resulted in enhanced sensitivity to drought stress. The transgenic lines exhibited higher leaf water loss, malondialdehyde and reactive oxygen species (ROS) content, and lower antioxidant enzyme activities after drought treatment than wild-type plants. Gene silencing of TaSPL6 enhanced the drought tolerance of wheat, as reflected by better growth status. Additionally, RNA-seq and qRT-PCR analyses revealed that TaSPL6-A functions by decreasing the expression of a number of genes involved in stress responses. These findings suggest that TaSPL6 acts as a negative regulator of drought stress responses in plants, which may have major implications for understanding and enhancing crop tolerance to environmental stresses.

Single-Cell RNA Sequencing Transcriptomics Revealed HCMV IE2-Related Microglia Responses in Alzheimer's-Like Disease in Transgenic Mice.

    Although multiple factors are known to concur with Alzheimer's disease (AD), the relationship between human cytomegalovirus (HCMV) and AD-like disease is unclear. Here, we propose a hypothesis that HCMV immediate-early 2 (IE2) protein promotes microglia activation and thus leads to AD-like disease. We successfully constructed IE2 transgenic mice expressing IE2 in the hippocampus. Single-cell sequencing analysis revealed that IE2 promoted the activation of microglia and upregulated the expression of disease-associated microglia genes. Differentially expressed gene analysis and pathway enrichment revealed that IE2 upregulated immune and nervous system disease-related genes. Immunohistochemical analysis showed that the expressions of both amyloid precursor protein (APP) and p-Tau were significantly upregulated in the brains of IE2 mice and were markers of AD. Taken together, these findings provide useful insights into AD-like disease activated by HCMV IE2.

ß-cell neogenesis: A rising star to rescue diabetes mellitus.

BACKGROUND: Diabetes Mellitus (DM), a chronic metabolic disease characterized by elevated blood glucose, is caused by various degrees of insulin resistance and dysfunctional insulin secretion, resulting in hyperglycemia. The loss and failure of functional ß-cells are key mechanisms resulting in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). AIM OF REVIEW: Elucidating the underlying mechanisms of ß-cell failure, and exploring approaches for ß-cell neogenesis to reverse ß-cell dysfunction may provide novel strategies for DM therapy. KEY SCIENTIFIC CONCEPTS OF REVIEW: Emerging studies reveal that genetic susceptibility, endoplasmic reticulum (ER) stress, oxidative stress, islet inflammation, and protein modification linked to multiple signaling pathways contribute to DM pathogenesis. Over the past few years, replenishing functional ß-cell by ß-cell neogenesis to restore the number and function of pancreatic ß-cells has remarkably exhibited a promising therapeutic approach for DM therapy. In this review, we provide a comprehensive overview of the underlying mechanisms of ß-cell failure in DM, highlight the effective approaches for ß-cell neogenesis, as well as discuss the current clinical and preclinical agents research advances of ß-cell neogenesis. Insights into the challenges of translating ß-cell neogenesis into clinical application for DM treatment are also offered.